ES2339997T3 - Metodo para producir compuestos de fenilalanina opticamente activos a partir de derivados de acido cinamico que emplea una fenilalanina amoniaco liasa derivada de idiomarina loihiensis. - Google Patents
Metodo para producir compuestos de fenilalanina opticamente activos a partir de derivados de acido cinamico que emplea una fenilalanina amoniaco liasa derivada de idiomarina loihiensis. Download PDFInfo
- Publication number
- ES2339997T3 ES2339997T3 ES07818125T ES07818125T ES2339997T3 ES 2339997 T3 ES2339997 T3 ES 2339997T3 ES 07818125 T ES07818125 T ES 07818125T ES 07818125 T ES07818125 T ES 07818125T ES 2339997 T3 ES2339997 T3 ES 2339997T3
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- Prior art keywords
- group
- phenylalanine
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- compound
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- Prior art date
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- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 239000002253 acid Substances 0.000 title claims description 11
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 title claims description 7
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 title description 21
- 229910021529 ammonia Inorganic materials 0.000 title description 5
- 150000002994 phenylalanines Chemical class 0.000 title 1
- 108700023158 Phenylalanine ammonia-lyases Proteins 0.000 claims abstract description 69
- 238000000034 method Methods 0.000 claims abstract description 50
- -1 phenylalanine compound Chemical class 0.000 claims abstract description 36
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 125000003277 amino group Chemical group 0.000 claims abstract description 13
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims abstract description 7
- 150000001413 amino acids Chemical group 0.000 claims abstract description 7
- 229930016911 cinnamic acid Natural products 0.000 claims abstract description 7
- 235000013985 cinnamic acid Nutrition 0.000 claims abstract description 7
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims abstract description 7
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 claims abstract description 6
- 230000000707 stereoselective effect Effects 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000001931 aliphatic group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- JFVLNTLXEZDFHW-QMMMGPOBSA-N (2s)-2-amino-3-(2-bromophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1Br JFVLNTLXEZDFHW-QMMMGPOBSA-N 0.000 claims description 6
- 125000002015 acyclic group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical group [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 5
- CVZZNRXMDCOHBG-QMMMGPOBSA-N 2-Chloro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1Cl CVZZNRXMDCOHBG-QMMMGPOBSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 150000001412 amines Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 3
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- QNRXNRGSOJZINA-UHFFFAOYSA-N indoline-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)CC2=C1 QNRXNRGSOJZINA-UHFFFAOYSA-N 0.000 claims description 3
- 150000002825 nitriles Chemical class 0.000 claims description 3
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 claims 1
- 150000001805 chlorine compounds Chemical group 0.000 claims 1
- 125000002560 nitrile group Chemical group 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims 1
- 230000000694 effects Effects 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 20
- 239000000758 substrate Substances 0.000 description 16
- 102000004190 Enzymes Human genes 0.000 description 14
- 108090000790 Enzymes Proteins 0.000 description 14
- 108020004414 DNA Proteins 0.000 description 13
- 241000223253 Rhodotorula glutinis Species 0.000 description 13
- 241000948245 Idiomarina loihiensis Species 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 11
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
- 241000588724 Escherichia coli Species 0.000 description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 241000605896 Fibrobacter succinogenes Species 0.000 description 5
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 5
- 241001223867 Shewanella oneidensis Species 0.000 description 5
- 241000607265 Vibrio vulnificus Species 0.000 description 5
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- LUFPJJNWMYZRQE-UHFFFAOYSA-N benzylsulfanylmethylbenzene Chemical compound C=1C=CC=CC=1CSCC1=CC=CC=C1 LUFPJJNWMYZRQE-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- 150000007523 nucleic acids Chemical group 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- OMHDOOAFLCMRFX-AATRIKPKSA-N (e)-3-(2-bromophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1Br OMHDOOAFLCMRFX-AATRIKPKSA-N 0.000 description 3
- CVZZNRXMDCOHBG-UHFFFAOYSA-N 2-azaniumyl-3-(2-chlorophenyl)propanoate Chemical compound OC(=O)C(N)CC1=CC=CC=C1Cl CVZZNRXMDCOHBG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000030789 Histidine Ammonia-Lyase Human genes 0.000 description 3
- 108700006308 Histidine ammonia-lyases Proteins 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 150000002993 phenylalanine derivatives Chemical class 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QNRXNRGSOJZINA-QMMMGPOBSA-N (2s)-2,3-dihydro-1h-indole-2-carboxylic acid Chemical compound C1=CC=C2N[C@H](C(=O)O)CC2=C1 QNRXNRGSOJZINA-QMMMGPOBSA-N 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical class OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
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- 239000007983 Tris buffer Substances 0.000 description 2
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- 229940024606 amino acid Drugs 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
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- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
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- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical class [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
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- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- WAEMQWOKJMHJLA-UHFFFAOYSA-N Manganese(2+) Chemical class [Mn+2] WAEMQWOKJMHJLA-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical class ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- 101100242548 Rhodosporidium toruloides PAL gene Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- UDGLQVQTIYLLLW-HNNXBMFYSA-N benzyl (2s)-2-amino-3-(2-iodophenyl)propanoate Chemical compound C([C@H](N)C(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1I UDGLQVQTIYLLLW-HNNXBMFYSA-N 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 1
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- 238000005119 centrifugation Methods 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- GYVDIWKDFAXBGV-JTQLQIEISA-N ethyl (2s)-2-amino-3-(2-chlorophenyl)propanoate Chemical compound CCOC(=O)[C@@H](N)CC1=CC=CC=C1Cl GYVDIWKDFAXBGV-JTQLQIEISA-N 0.000 description 1
- KPRQQLUZKQSWAZ-JTQLQIEISA-N ethyl (2s)-2-amino-3-(2-iodophenyl)propanoate Chemical compound CCOC(=O)[C@@H](N)CC1=CC=CC=C1I KPRQQLUZKQSWAZ-JTQLQIEISA-N 0.000 description 1
- SRZGZYFLLSBJSE-UHFFFAOYSA-N ethyl 2-amino-3-(2-bromophenyl)propanoate Chemical compound CCOC(=O)C(N)CC1=CC=CC=C1Br SRZGZYFLLSBJSE-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000012239 gene modification Methods 0.000 description 1
- 230000005017 genetic modification Effects 0.000 description 1
- 235000013617 genetically modified food Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 229950009810 indolapril Drugs 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229910052751 metal Chemical class 0.000 description 1
- 239000002184 metal Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- MBKCAPHZXHQJNI-VIFPVBQESA-N methyl (2s)-2-amino-3-(2-bromophenyl)propanoate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1Br MBKCAPHZXHQJNI-VIFPVBQESA-N 0.000 description 1
- BSFAOUNWBLVIKZ-VIFPVBQESA-N methyl (2s)-2-amino-3-(2-chlorophenyl)propanoate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1Cl BSFAOUNWBLVIKZ-VIFPVBQESA-N 0.000 description 1
- CNFGADUGLUGHKQ-VIFPVBQESA-N methyl (2s)-2-amino-3-(2-iodophenyl)propanoate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1I CNFGADUGLUGHKQ-VIFPVBQESA-N 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000001272 nitrous oxide Substances 0.000 description 1
- 125000005492 nosylate group Chemical group 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229950008492 pentopril Drugs 0.000 description 1
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
- 229960002582 perindopril Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical class OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
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- 125000005490 tosylate group Chemical group 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
- C12P13/22—Tryptophan; Tyrosine; Phenylalanine; 3,4-Dihydroxyphenylalanine
- C12P13/222—Phenylalanine
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06019071 | 2006-09-12 | ||
| EP06019071 | 2006-09-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2339997T3 true ES2339997T3 (es) | 2010-05-27 |
Family
ID=37692640
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES07818125T Active ES2339997T3 (es) | 2006-09-12 | 2007-09-12 | Metodo para producir compuestos de fenilalanina opticamente activos a partir de derivados de acido cinamico que emplea una fenilalanina amoniaco liasa derivada de idiomarina loihiensis. |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP2069518B1 (de) |
| CN (2) | CN105238825B (de) |
| AT (1) | ATE457035T1 (de) |
| DE (1) | DE602007004678D1 (de) |
| EA (1) | EA015803B1 (de) |
| ES (1) | ES2339997T3 (de) |
| WO (1) | WO2008031578A1 (de) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106755160B (zh) * | 2017-01-17 | 2019-08-02 | 湖州颐辉生物科技有限公司 | 一种组氨酸解氨酶及其用途 |
| CN115354035B (zh) * | 2022-04-28 | 2023-07-04 | 中国热带农业科学院热带作物品种资源研究所 | 一种柱花草苯丙氨酸解氨酶SgPAL2及其编码基因和应用 |
| CN116949024B (zh) * | 2023-07-24 | 2024-08-02 | 江南大学 | 一种苯丙氨酸解氨酶突变体及其在合成（s）-2-氯-苯丙氨酸中的应用 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5981239A (en) * | 1997-09-24 | 1999-11-09 | Great Lakes Chemical Corp. | Synthesis of optically active phenylalanine analogs using Rhodotorula graminis |
| EP1833789B1 (de) * | 2004-12-28 | 2011-07-06 | DSM IP Assets B.V. | Verfahren zur herstellung von enantiomerenangereicherter indolin-2-carbonsäure |
-
2007
- 2007-09-12 CN CN201510536561.8A patent/CN105238825B/zh not_active Expired - Fee Related
- 2007-09-12 ES ES07818125T patent/ES2339997T3/es active Active
- 2007-09-12 DE DE602007004678T patent/DE602007004678D1/de active Active
- 2007-09-12 EA EA200900430A patent/EA015803B1/ru not_active IP Right Cessation
- 2007-09-12 WO PCT/EP2007/007945 patent/WO2008031578A1/en not_active Ceased
- 2007-09-12 EP EP07818125A patent/EP2069518B1/de not_active Not-in-force
- 2007-09-12 AT AT07818125T patent/ATE457035T1/de active
- 2007-09-12 CN CNA2007800338158A patent/CN101517089A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DE602007004678D1 (de) | 2010-03-25 |
| CN105238825A (zh) | 2016-01-13 |
| WO2008031578A1 (en) | 2008-03-20 |
| CN101517089A (zh) | 2009-08-26 |
| EA015803B1 (ru) | 2011-12-30 |
| CN105238825B (zh) | 2019-01-04 |
| EA200900430A1 (ru) | 2009-08-28 |
| EP2069518B1 (de) | 2010-02-03 |
| ATE457035T1 (de) | 2010-02-15 |
| EP2069518A1 (de) | 2009-06-17 |
| HK1219507A1 (zh) | 2017-04-07 |
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